| #608612 | |||||||||||||||
| MANDIBULOACRAL DYSPLASIA WITH TYPE B LIPODYSTROPHY; MADB | |||||||||||||||
| Alternative titles; symbols | |||||||||||||||
| LIPODYSTROPHY, TYPE B, ASSOCIATED WITH MANDIBULOACRAL DYSPLASIA | |||||||||||||||
| Phenotype Gene Relationships | |||||||||||||||
| |||||||||||||||
| Clinical Synopsis | |||||||||||||||
| TEXT | |||||||||||||||
| A number sign (#) is used with this entry because mandibuloacral dysplasia with type B lipodystrophy can be caused by mutation in the ZMPSTE24 gene (606480). For a general phenotypic description of lipodystrophy associated with mandibuloacral dysplasia, see MADA (248370). | |||||||||||||||
| Clinical Features | |||||||||||||||
| Schrander-Stumpel et al. (1992) reported a girl who presented at birth with a small chin, small nose and mouth, retrognathia, and thin facial skin. By age 2 years, her skin was very thin and tense on her limbs, resulting in contractures and poor wound healing. She had several skeletal anomalies, including delayed closure of the fontanels and multiple wormian bones, hypoplastic clavicles, short terminal phalanges with acroosteolysis. Other features included poorly implanted teeth, scarce, brittle hair, mottled pigmentation, and broad, dysplastic nails. She also had multiple hard nodules consisting of sclerotic calcified tissue on the hands and feet and other areas of the body. In a follow-up report of the same patient, Agarwal et al. (2003) noted that the patient had generalized lipodystrophy affecting the extremities, the trunk, and the face, which contributed to the 'progeroid' appearance. Simha and Garg (2002) studied body fat distribution in 2 male and 2 female patients with MAD by anthropometry, dual energy x-ray absorptiometry, and magnetic resonance imaging. Three of the 4 subjects had loss of subcutaneous fat from the extremities with normal or slight excess in the neck and truncal regions (termed type A pattern). In contrast, 1 patient had generalized loss of subcutaneous fat involving the face, trunk, and extremities (type B pattern). All of the patients had normal glucose tolerance, but had fasting and postprandial hyperinsulinemia suggestive of insulin resistance. Elevated serum triglycerides with low high density lipoprotein cholesterol levels were noted in 3 subjects. The authors concluded that MAD presents with 2 types of body fat distribution patterns, both of which are associated with insulin resistance and its metabolic complications. Miyoshi et al. (2008) reported 2 Japanese sisters, ages 7 and 3 years, with MAD. Both had the classic facial phenotype with mandibular hypoplasia, prominent eyes, beaked nose, and dental overcrowding. Other classic features included atrophic skin, mottled hyperpigmentation, fractured clavicle in 1, acroosteolysis, joint contractures, and generalized loss of subcutaneous adipose tissue. The older sister had lipodystrophy affecting the chest and thighs, but sparing the abdomen. Endocrine studies were essentially normal. | |||||||||||||||
| Molecular Genetics | |||||||||||||||
| In 4 families with MAD and type B lipodystrophy, Simha et al. (2003) did not identify mutations in several genes associated with other forms of lipodystrophy, including LMNA (150330), AGPAT2 (603100), seipin (606158), and PPARG (601487). In a woman with MAD and generalized lipodystrophy first reported by Schrander-Stumpel et al. (1992), Agarwal et al. (2003) identified compound heterozygosity for 2 mutations in the ZMPSTE24 gene (606480.0001 and 606480.0002). The unaffected parents and 2 unaffected sibs of the patients were heterozygous for 1 of the mutations. In 2 Japanese sisters with severe MAD, Miyoshi et al. (2008) identified compound heterozygous mutations in the ZMPSTE24 gene (606480.0004 and 606480.0005). | |||||||||||||||
| REFERENCES | |||||||||||||||
| |||||||||||||||
| |||||||||||||||